Novel drug delivery technology

ABSTRACT

The invention relates to a novel drug delivery technology. More particularly the invention relates to a method of delivering at least one therapeutic compound or a formulation comprising the at least one therapeutic compound to a patient; to a throwaway or reusable device for delivering at least one therapeutic compound or a formulation comprising the at least one therapeutic compound to a patient in a manner as set out by the method; to a pioneer projectile for use in said method; to formulations for use in said method and to an injectate comprising a pioneer projectile and formulation. It also relates to a disposable component containing either a pioneer projectile or an injectate. The invention also relates to a throwaway or reusable device for delivering at least one therapeutic compound, or a formulation comprising the at least one therapeutic compound (hereafter drug) to a patient, and a method for administering a drug to a patient using said device. It also relates to a packaged drug for use with said device.

This application is a divisional of Ser. No. 11/633,804 (allowed), whichwas filed on Dec. 5, 2006 (published as US 2007-0275044-A1 on Nov. 29,2007), which is a continuation of Ser. No. 10/238,415 (now U.S. PatentNo. 7,615,234), filed Sep. 10, 2002, and further claims benefit of UKApplication No. 0218126.1, filed Aug. 5, 2002 and UK Application No.0121914.6, filed Sep. 11, 2001, the entire contents of each of which arehereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to a novel drug delivery technology. Moreparticularly the invention relates to a method of delivering at leastone therapeutic compound or a formulation comprising the at least onetherapeutic compound to a patient; to a throwaway or reusable device fordelivering at least one therapeutic compound or a formulation comprisingthe at least one therapeutic compound to a patient in a manner as setout by the method; to a pioneer projectile for use in said method; toformulations for use in said method and to an injectate comprising apioneer projectile and formulation. It also relates to a disposablecomponent containing either a pioneer projectile or an injectate. Thepresent invention also relates to a throwaway or reusable device fordelivering at least one therapeutic compound, or a formulationcomprising the at least one therapeutic compound (hereafter drug) to apatient, and a method for administering a drug to a patient using saiddevice. It also relates to a packaged drug for use with said device.

BACKGROUND TO THE INVENTION

One route of administration for therapeutic compounds is through theskin. The skin is also one of the more efficient routes for delivery ofa therapeutic compound when compared to other standard delivery routessuch as oral or pulmonary delivery.

Administration to the skin is most commonly undertaken using a needleand syringe as a delivery system with the therapeutic compound in aliquid form.

Such a system has a number of associated problems including the pain andfear associated with needles, the fact they are really best suited toinjecting liquids which are not necessarily the best way of deliveringcompounds to a patient and the fact that sharps are left which create adisposal problem.

Drug delivery systems that do not incorporate needles are also used forinjecting liquids through the skin and this is achieved by the deliverysystem creating a very fine, high velocity liquid jet that creates itsown hole through the skin. There are however a number of problems withsuch a method including splash back.

With both these forms of liquid delivery relatively large volumes ofliquid are injected which, because they are incompressible, have to tearthe tissue apart in order to be accommodated.

However, drug injection through the skin does not have to be achievedwith the drug in a standard liquid form. Solid form drugs have beensuccessfully administered with the PowderJect system, which uses acompressed gas source to accelerate powdered drugs to a velocity atwhich they can penetrate the outer layers of the skin. This systemtypically employs powdered drug particles of less than 100 microns indiameter, which require a velocity of several hundred metres per secondin order to penetrate human tissue. However the system has its owninherent problems such as controlled delivery.

It has also been shown in the past that solid rods or splinters of atherapeutic compound can be pushed, at a relatively low velocity, intothe skin without the requirement for a needle although moretraditionally these are delivered as implants.

The current transdermal drug delivery techniques can thus be categorisedinto groups based on the drug form and the velocity of the injection asset out in table 1 below:

TABLE 1 Drug Form Drug Injection Velocity Liquid Solid High VelocityLiquid Jet Injector PowderJect Systems Drug darts Low Velocity Needleand Syringe Drug ‘Splinters’

Drug darts are disclosed in a number of publications. WO 96/40351(American Cyanamid) discloses an implant dart with a head of a solidplastics material which takes the form of a blade and a tubular bodythat contains one or more sustained release drug delivery implantpackages. Flexible stabilizing wings are provided on either side of thedart head which serve as a lock or barb to prevent the dart being pulledout after entry. The dart has on outside diameter of about 7 mm and alength of about 45 mm and is delivered with an injection gun which firesthe dart into an animal, but not a human, when a trigger is released.The propulsion mechanism delivers a force sufficient to impart a highaccelerating velocity of from 40-60 mph on the dart. To inject the dartat low speed it is necessary to make a small incision in the animal andoperate the push bar manually.

U.S. Pat. No. 3,948,263 and U.S. Pat. No. 4,326,524 also discloseballistic delivery devices. U.S. Pat. No. 3,948,263 discloses aballistic implant which is fired from a 0.25 calibre rifle. Theprojectile exits at about 900 ft/sec and can travel 20-40 ft beforeimplanting into muscle some 1-2 inches beneath the skin. U.S. Pat.No.4,326,524 discloses a solid dose ballistic projectile formed entirelyof a cohesive mixture comprising biologically active material, in theform of grindable solid particles and a binder which is capable ofwithstanding the stresses imparted on impact. The projectile has a bodyportion with a diameter of from 4.5 to 7.6 mm, with a conical noseportion with a base diameter smaller than the diameter of the body suchthat a slight shoulder region is formed between the body and the nose.The end remote from the nose is preferably concave to aid flight.

GB 2365100 is another example of a remote ballistic delivery devicewhich is fired and attains velocities of greater than 500m/s. Incontrast to those described above the device is slowed on impact so thatit does not enter the body but instead the device's nose is moved backsuch that a needle enters the body, and a drug is injected. Such adevice is not needleless.

CA1019638 discloses a projectile which is launched by a conventional airgun or bow. It comprises a head piece and a shaft, the head piecepierces the animals flesh and the shaft breaks away. In one embodimentthe head piece is made of a porous material which retains a liquid drugthrough capillary action through launch and impact and which releases itby diffusion when it is inserted into the animal. In a second embodimentthe head piece takes the form of a hardened cake. To aid penetration ametal or plastics tip may be provided. The drug delivering elementremaining in the skin is about 3 mm diameter by 13 mm in length.

U.S. Pat. No. 3,901,158 Ferb discloses a hypodermic projectile which isagain fired from a rifle or pistol. It comprises a shatterable front endof plastic or glass which breaks on impact releasing the liquidcontents.

None of the described high velocity devices bear any resemblance to thepresent invention in which the at least one therapeutic compound or aformulation comprising the at least one therapeutic compound is pushedat low velocity from a device which contacts the skin and in which thepioneer projectile is water soluble, lipid soluble or otherwisebiodegradable in the human or animal and is furthermore significantlysmaller having a width or diameter of less than 3 mm in width, morepreferably still less than 2.5 mm through 2 mm and 1.5 mm to about 1 mmin width; a height of less than 10 mm in height, more preferably about1.5 to 2 mm in height and an aspect ratio of less than 1:8, preferablyless than 1:6, more preferably less than 1:4, more preferably still lessthan 1:3, and most preferably about 1:1.5.

High velocity liquid systems are exemplified by U.S. Pat. No. 116,313 McGregor. Liquid is first ejected from a small orifice in a probe at avery high velocity and pressure which will penetrate the skin and thenthe main charge of liquid is ejected at a lower velocity into thechannel formed by the initial penetration.

EP0139286 (Sumitomo Chemical Co Limited) discloses sustained-releasepreparations in the form of needle like or bar like shapes, whichcomprise an active ingredient and a pharmaceutically acceptablebiodegradable carrier. The sustained-release preparation can beadministered to the body by injection by pushing it through a hollowneedle or by implantation.

WO 94/22423 (Bukh Meditec AIS) discloses a drug administration system.The method of parenteral administration comprises administering a drugsubstance by penetrating the skin or the mucosa of a human or an animalby a body with an appropriately formed solid pharmaceutical composition.The body of the pharmaceutical composition may be needle shaped so as toavoid external penetration equipment. The solid pharmaceuticalcomposition comprises at least one drug substance and has a shape and/orstrength to enable penetration. The composition is made by mixing amaterial, preferably a polymer and optionally a filler with an activedrug substance; extruding the mixture to form an elongate body; dryingit and forming a pointed end.

U.S. Pat. No. 5,542,920, U.S. Pat. No. 6,117,443 and U.S. Pat. No.6,120,786 (Cherif Cheikh) all disclose needle-less parenteralintroduction devices. A medicament is made in the form of a solid needlehaving a pointed end that has sufficient structural integrity topenetrate the skin. The needles are less than 2 mm, preferably 0.2 to0.8 mm, in diameter and 10 to 30 mm in length.

U.S. Pat. No. 6,102,896 (Roser) is primarily directed to a disposableinjector device for injecting controlled release water soluble glassneedles. It however also recognises that these glass needles, which areabout 1 mm in diameter by 10 mm in length and contain a medicament mayalso be used as pioneer projectiles to produce a low resistance pathwaythrough the tissue along which a liquid suspension (exemplified as adrug in a suspension of PFC fluid) can flow. This document appears thefirst and only document to recognise that a dissolvable pioneerprojectile may be used to enable the introduction of a medicament. Ithowever fails to recognise that it may be used as a general techniquefor introducing medicaments in other forms. Indeed this is readilyapparent from the document in which a dry powdered formulation is madeinto a non viscous liquid by suspending it in PFC.

SUMMARY OF THE INVENTION

The present invention takes the concept of using a pioneer projection(as disclosed in U.S. Pat. No. 6,102,896) further and follows from theapplicants recognition that a pioneer projectile can be used as a meansfor introducing medicaments in forms other than a free flowing, nonviscous liquid.

According to a first aspect of the present invention there is provided amethod of delivering at least one therapeutic compound or a formulationcontaining the at least one therapeutic compound to a human or animal inthe form of a needleless injection comprising:

-   -   i) Penetrating the skin with a water soluble, lipid soluble or        otherwise biodegradable pioneer projectile having a diameter of        less than 3 mm which is left in the human or animal; and    -   ii) Introducing directly, or substantially directly, behind the        pioneer projectile, the at least one therapeutic compound or the        formulation containing the at least one therapeutic compound,        which at least one therapeutic compound or the formulation        containing the at least one therapeutic compound is provided and        delivered in a contained state.

By contained state is meant either:

-   -   i) As a liquid contained by a membrane;    -   ii) As a liquid with a viscosity of at least 5000 centipoises        (the viscosity of honey), more particularly at least 50,000 (the        consistency of mayonnaise) and most preferably still at least        100,000 (the consistency of peanut butter), such that the liquid        has characteristics more akin to a solid than a liquid i.e. they        have a definite shape as well as volume (and are not readily        free flowing);    -   iii) As a semi-solid (having a viscosity and rigidity        intermediate that of a solid or a liquid);    -   iv) As a paste (having a soft malleable consistency);    -   v) As a gel (a liquid dispersed in a solid) which materials can        all be considered to have a degree of stiffness; or    -   vi) As a solid (a state in which the matter retains its own        shape).

Introducing a medicament in such a contained state has advantages inthat splash back and seepage can be avoided and more controlled dosagesdelivered when compared to a following non viscous liquid formulation.The viscous, semi solid or solid nature of the medicament ensures thatthe pioneer projectile is pushed to the requisite depth and is followedby the medicament rather than seeping around the sides of theprojectile. The semi solid formulations, gels, pastes and solids arealso generally more stable than liquid formulations and are more patientcompliable.

Furthermore it will be appreciated that by introducing the medicament ina form other than as a non viscous liquid behind a pioneer projectile itis possible to tailor the characteristics of the medicament for optimumpharmacokinetic delivery rather than for penetration.

Similarly the pioneer projectile can be developed to have optimisedpenetrating capabilities independent of the medicament.

Preferably the pioneer projectile is independent of the at least onetherapeutic compound or the formulation containing the at least onetherapeutic compound.

Alternatively the pioneer projectile is independent of yet forms anintegral part of the at least one therapeutic compound or theformulation containing the at least one therapeutic compound.

Most preferably the pioneer projectile forms a head to the at least onetherapeutic compound or the formulation containing the at least onetherapeutic compound.

The at least one therapeutic compound or the formulation containing theat least one therapeutic compound can take a number of forms.

In one embodiment the at least one therapeutic compound or theformulation containing the at least one therapeutic compound is a liquidcontained in a water soluble, lipid soluble or otherwise biodegradablemembrane.

In another embodiment the at least one therapeutic compound or theformulation containing the at least one therapeutic compound is providedin a solid form such as, for example, crystals, particles, granules,beads, rods, discs or a combination thereof.

In yet another embodiment the at least one therapeutic compound or theformulation containing the at least one therapeutic compound is providedas a viscous liquid, semi solid, gel or paste which may be furthersupported, if desirable, by a water soluble lipid soluble or otherwisebiodegradable membrane.

In the method of the invention the skin is penetrated and thetherapeutic compound administered at a low velocity. By low velocity ismeant less than 100 m/s. Preferably the velocity is less than 10 m/s,more preferably still less than 5 m/s and most preferably in the orderof a few m/s.

Since the injectate is pushed at a low velocity rather than fired at ahigh velocity it is possible to ensure that the dosage is alwaysdelivered to the correct (and same) depth under the skin. This meansthat the system can be used on different skin types and skin locationsand the dosage will still be delivered to the same depth.

According to a second aspect of the invention there is provided a methodof facilitating the delivery of at least one therapeutic compound or aformulation containing the at least one therapeutic compound to a humanor animal as a needleless injection comprising:

-   -   i) Providing a water soluble, lipid soluble or otherwise        biodegradable pioneer projectile having a diameter of less than        3 mm capable of penetrating the human or animals skin; and    -   ii) Providing directly, or substantially directly, behind the        pioneer projectile, the at least one therapeutic compound or the        formulation containing the at least one therapeutic compound in        a contained state.

The act of pushing the at least one therapeutic compound in thecontained state causes the pioneer projectile to penetrate the human oranimals skin and the therapeutic compound or the formulation containingthe at least one therapeutic compound follows the pioneer projectile andis introduced into the human or animal in the contained state.

The invention also extends to novel pioneer projectiles.

According to a third aspect of the present invention there is provided awater soluble, lipid soluble or otherwise biodegradable pioneerprojectile having a diameter of less than 3 mm, and which is capable ofpenetrating the skin of a human or animal to thereby facilitate theinjection of at least one following therapeutic compound or therapeuticcompound containing formulation in a contained state, comprising:

-   -   i) A first “penetrating” face which in use penetrates the human        or animals skin; and    -   ii) Remote from the first face a second “driven” face which in        the course of injection is the face upon which a driving force        is exerted through the contained therapeutic compound or        therapeutic compound containing formulation; characterised in        that said pioneer projectile has an aspect ratio (width to        height) of less than 1:10.

Because the pioneer projectile has been developed separately of themedication it has been possible to reduce its size from one of at least10 mm in length to about a few millimetres. It has also been possible tooptimise its shape such that it functions as a leading head or tip for afollowing contained formulation, the two components forming aninjectate.

Preferably the pioneer projectile has an aspect ratio of less than 1:8,preferably less than 1:6, more preferably less than 1:4, more preferablystill less than 1:3, and most preferably about 1:1.5.

Preferably the pioneer projectile is less than 3 mm in width, morepreferably still less than 2.5 mm, through 2 mm and 1.5 mm, to about 1mm in width.

Preferably the pioneer is less than 10 mm in height, more preferablyabout 1.5 to 2 mm in height. By reducing the height to a minimum it ispossible to maximise the amount of therapeutic compound being injected.In this regard it should be noted that if the combined pioneerprojectile and following drug formulation is too long it might not bepossible to deliver the drug to the optimum depth.

In one embodiment the pioneer projectile is free of any therapeuticcompound. In another embodiment it comprises at least one therapeuticcompound. Thus, for example it might be beneficial to include, forexample, an antibiotic in the pioneer projectile or have it release atherapeutic compound at a different rate to the formulation in, forexample, the case of insulin injections.

The skin penetrating face of the pioneer projectile preferably comprisesa cutting element to facilitate entry. This may take the form of a sharppoint or an oblique edge. Alternatively the skin penetrating face may beblunt or gently curved.

In one embodiment the face for contacting the therapeutic compound ortherapeutic compound containing formulation in a contained state isflat. Alternatively it may be concave or otherwise hollowed tofacilitate pushing and formulation containment.

The pioneer projectile may be made of any suitable material. Suitablematerials are those hard and rigid enough to facilitate penetration atlow velocities. Preferred materials include glassy materials e.g. thesugar glasses as noted in WO 98/41188 which materials are includedherein by reference. The term “sugar” thus covers not only disaccharidesugars, such as, trehalose, but also monosaccharide sugars and their nonreducing derivatives, such as, sugar alcohols including: mannitol,inositol, xylitol, ribitol and the like, which form a general class ofstabilising glass-forming sugars and sugar derivatives. The term “sugarglass” is to be understood as covering not only glasses which arereadily and rapidly dissolved in an aqueous environment, such as,trehalose but also sugar glasses in which the sugar molecule has beenmodified by the attachment of one or more hydrophobic side chains tomake the glass more slowly soluble in bodily fluids than the nativesugar in order to give controlled release characteristics.

In some circumstances the pioneer projectile may comprise a barriermaterial over at least the face that contacts the therapeutic compoundin a contained state or vice versa such that the respective componentswill not react with one another.

The invention also extends to novel formulations.

According to a fourth aspect of the present invention there is provideda therapeutic compound or therapeutic compound containing formulationwhich is held in a contained state and adapted for introduction into ahuman or animal in the form of a needleless injection behind a watersoluble, lipid soluble or otherwise biodegradable pioneer projectilehaving a diameter of less than 3 mm.

Preferably the formulation comprises less than 50 mg of therapeuticcompound in a volume of less than 50 mm³, more preferably less than 10mg of therapeutic compound in a volume of less than 10 mm³.

The therapeutic compound or therapeutic compound containing formulationmay be provided as a liquid contained in water soluble, lipid soluble orotherwise biodegradable membrane.

In an alternative embodiment the therapeutic compound or therapeuticcompound containing formulation is provided in a solid form comprisingfor example crystals, particles, granules, beads, rods, discs or acombination thereof which are generally likely to be more stable thantraditional non-viscous liquid formulations with a viscosity similar tothat of water e.g. 1 Centipoise or glucose e.g. 500 Centipoises.

In a preferred embodiment the therapeutic compound or therapeuticcompound containing formulation is provided as a semi solid, gel orpaste. In this form it is particularly patient compliant and thetherapeutic compound is generally likely to be more stable than if itwere in a traditional non-viscous liquid formulation.

Where the therapeutic compound or therapeutic compound containingformulation is a viscous liquid, it preferably has a viscosity of atleast 10,000 Centipoises more preferably at least 50,000 Centipoises andmore preferably still at least 100,000 Centipoises.

The formulation may comprise an end piece beyond the therapeuticcompound or therapeutic compound which is free of the “active” beinginjected thus ensuring that the entire therapeutic compound enters thepatient in a unit dose rather than risk under or over dosing.

The therapeutic compound or therapeutic compound containing formulationmay comprise a plurality of differently formulated elements.

The therapeutic compound or therapeutic compound containing formulationmay be packaged in a cap, cartridge, carousel or cassette.

The invention also extends to an injectate comprising a pioneerprojectile and a therapeutic compound or therapeutic compound containingformulation.

According to a fifth aspect of the present invention there is provided aneedleless injectate for injection comprising:

-   -   a) A water soluble, lipid soluble or otherwise biodegradable        pioneer projectile having a diameter of less than 3 mm; and    -   b) A therapeutic compound or therapeutic compound containing        formulation which is held in a contained state behind the        pioneer projectile.

These components are as previously described.

The pioneer projectile and therapeutic compound or therapeutic compoundcontaining formulation may both be water soluble, lipid soluble orotherwise biodegradable to differing degrees.

A barrier may be provided between the pioneer projectile and thetherapeutic compound or therapeutic compound containing formulation.

The injectate may be contained/packaged in a cap, cartridge, carousel orcassette optionally together with a means, e.g. an ejector pin, forpushing the injectate out of its container.

Alternatively the pioneer projectile and the therapeutic compound ortherapeutic compound containing formulation are contained/packaged inseparate caps, cartridges, carousels or cassettes.

The invention also extends to a device for injecting a pioneerprojectile and a therapeutic compound or therapeutic compound containingformulation.

According to a sixth aspect of the present invention there is provided aneedleless device (60) for injecting a water soluble, lipid soluble orotherwise biodegradable pioneer projectile (10) having a diameter ofless than 3 mm and at least one contained therapeutic compound ortherapeutic compound containing formulation (42) into a human or animalbody, said device comprises a housing (62) containing a mechanism (92)capable of generating a force which will cause a striker (84) to travelalong a striker guide (86), said housing having an end face (100) whichis in operative communication with a component (72) comprising a casing(74) having an aperture (76) in which is mounted an ejector pin (78)and, therebelow, an injectate (40) comprising a pioneer projectile (10)and a formulation (42) such that in use the striker will contact theejector pin and the injectate will be pushed out of the casing as asingle unit into the human or animal body.

The reference numerals given above are non-limiting but have beenincluded solely for the purpose of assisting the reader.

The term ejector pin is intented to cover a pin, piston, rod or likemember which functions to push the injectate from the aperture.

The power source for initiating or assisting the pushing may be amechanical spring in the form of, for example, a coiled spring or alever spring. Alternatively, a gas spring might be used or even anelectrically powered system. A mechanical spring would allow reuse ofthe delivery system although this would mean the user has to rechargethe spring between administrations. Alternatively, the spring(mechanical or gas) could be pre-charged during manufacture so that itcan only be used once and then the whole system would be thrown away. Ina reusable device there will be a throw away component containing thepioneer projectile or the pioneer projectile and the therapeuticcompound or therapeutic compound containing formulation.

The device preferably incorporates a safety mechanism to avoidaccidental actuation. Actuation might be triggered with a push button onthe device but preferably would be undertaken by pushing the deviceagainst the skin thus ensuring good contact with the skin on actuation.

In a reusable device the reusable component and the throw away componentcomprise means by which they are connected to one another.

The device may be adapted to inject multiple doses either sequentiallyor simultaneously. In one embodiment the device comprises a cartridge,carousel or cassette containing a plurality of pioneer projectiles or aplurality of injectates comprising a pioneer projectile and atherapeutic compound or therapeutic compound containing formulation.

In another embodiment the device comprises a cap containing a singlepioneer projectile and a single unit dose of the therapeutic compound ortherapeutic compound containing formulation.

The various aspects described above give rise to a system having anumber of advantages over the prior art delivery methods and some ofthese are noted in table 2 below:

TABLE 2 Benefit Justification 1 Can use Many drugs are more stable insolid form formulations with than in a liquid state. A viscous liquidIncreased Product formulation would be more akin to a solid Stability.drug in terms of its stability characteristics because of the excipientsthat can be used 2 Improved Product The increased stability with someStorage compounds may allow storage of the final delivery system at roomtemperature rather than requiring refrigeration 3 Reduced Risk OfWithout the need for needles there is a Cross Infection reduced risk ofblood borne diseases 4 Small Device Size Spring, trigger, injectate andpiston are the main components required 5 Cheap Device A spring is acheap power source. Small overall number of device components 6 ReusableDevice The design can allow for the spring to be primed for reuse.Disposable components would be small in terms of size and cost but wouldinclude the component holding the injectate or pioneer projectile 7Variable Power A spring-powered device could allow the System tension onthe spring to be altered for different skin types and skin positions onthe body, if necessary. 8 Small Skin As experienced with splintersResponse 9 Quiet Device Actuation of a spring powered delivery systemwill be quiet 10 Easy to Understand Easy to comprehend the forcesinvolved Delivery System in pushing a foreign body into the skin to aknown depth. Easy to measure the physical characteristics required for a‘dose’ of injectate of this size 11 Variable Dose With a viscousinjectate it will be possible to alter the dose injected 12 SelfInjection With a simple system patients can inject themselves, thusreducing healthcare costs 13 Controlled Depth Pushing the injectate intothe skin rather Of Penetration than firing it enables a consistent andOf The Delivered controlled depth of penetration in the skin Dose 14Large Doses Large doses of one or more drugs are Achievable achievableby having one or more doses of injectate administered in the sameinjection

The concept behind the invention allows for a simple needleless drugdelivery device that pushes a drug in a “contained” state.

A semi solid, paste or gel is the preferred form since unlike anon-viscous liquid it would follow the pioneer projectile. (Anon-viscous liquid can “splash back” and more easily seep around thetrack formed by the pioneer projectile.) Its stiffness relative to anon-viscous liquid also means it is easier to push than a non-viscousliquid material. The more solid in nature the better this is. Howeverfrom a comfort perspective a semi solid or paste or gel is more likelyto be patient compliant and dissolve more readily in the body.

The delivery device for delivering such an injectate (pioneer projectileand formulation) could take a number of forms and several such devicesare described by way of example.

A first device described is a spring-powered device with the spring,triggering the pushing of a pin. The pin then engages the injectate topush it into the skin with the pin being stopped by either an end stopwithin the device or by coming into contact with the skin, preferablyover a relatively wide area (compared to the injectate) to reduce theforce felt on the skin.

If the device is to be reusable then the component holding the injectatemight be detached from the rest of the device and thrown away and a newdisposable component attached before the next injection. The injectionitself would occur in a matter of milliseconds after actuation and wouldseem instantaneous as far as the user is concerned. Alternatively theformulation might be injected from, for example, a tube and a newpioneer projectile would be required for a further injection.

By way of a further development the needleless device described withreference to the sixth aspect of the invention was further developedwith the aim of producing a simple, cheap drug delivery device which isadaptable and able to deliver a drug in the form of not only aneedleless injectate but also other forms, such as, for example liquidformulations, and solid drug needles.

This aim is achieved by the provision of a device which is adapted toreceive a packaged drug which is slidably mounted in the device suchthat in use the device is able to push the drug from its packaging, thepackaged drug being packaged such that the drug, whatever it's form, canbe pushed from its packaging by the device.

It is another and independent aim to package different drug forms foruse with such a device.

This aim is achieved by the provision of a packaging adapted to beattached to the device and which comprises a channel housing the drug,and a drive pin or like element for pushing it out when actuated by thedevice.

There are many possible product applications for such a delivery deviceand they include therapeutic, prophylactic and diagnostic applications.Applications may be limited to those drugs that are administered inrelatively low doses because of the dose limitations for each injectionimposed by pushing. However, although each dose may be limited to lessthan 10 mg or a volume of less than 10 mm³ it would be possible toadminister more than one dose either concurrently or sequentially, iflarger doses are required.

New laws in many states in the USA are declaring that safety needlesmust be used for injections whenever possible. These are needles thatwithdraw into a sheath as the needle is withdrawn from the patient sothat the needle tip is not left exposed. This is to avoid the use of aconventional needle which can result in accidental needle stickinjuries. A delivery system that either does not require a needle (orthat incorporates a needle that retracts) would be beneficial for the USmarket as well as other parts of the world that will, no doubt, followthe lead of the Americans.

Particular applications where the technology might be very well suitedinclude:

Vaccines:—Vaccinations are one of the common reasons for people to needan injection and many people would rather risk catching a disease thanhave to be injected with a standard needle and syringe. Children inparticular can often have a needle phobia. Therefore a system thateither does not incorporate a needle (or the needle is never seen by thepatient) might help compliance with vaccines. In third world countriesthere is a great need for delivery systems for vaccines that do notinvolve needles. An added advantage of the new delivery system is thatusing a non liquid dose therapeutic compound should assist stability ofthe active compounds and therefore the cold chain storage requirementsfor the vaccine may be avoided.

Acute Emergencies:—The device is very quick and easy to use andtherefore well suited for self administration as well as administrationby an untrained assistant. There are a number of drugs, such as glucagon(hypoglycaemia), migraine treatments or adrenalin (anaphylactic shock)that are required when the patient may not be in a suitable condition toundertake the injection themselves. Glucagon and some of the migrainetreatments are normally supplied as a powder that have to be made upwith the diluent before the injection which means that they are notsuitable for administration by an untrained assistant. In addition, thepatient may, or may not be in a fit state to make up the drug let aloneadminister it. The present device would enable these and similar drugsto be administered in solid dosage form.

Diabetes:—Millions of people worldwide have to inject insulin eitherdaily or several times a day. Most have to use a needle and syringealthough new delivery systems such as inhalers and insulin pumps arebecoming more popular. The advantage of the new delivery system is thatseveral different types of insulin can be administered in a solid doseform at one time. This can be done by having two or more short pieces ofdifferent insulin formulations in e.g. a drug cassette. This could allowa short as well as a long acting insulin to be injected at the same timeand thus reduce the requirement for multiple injections throughout theday.

Although the applications above have been highlighted, the technology issuitable for administering many drugs that are required at the dosagelevels capable of being delivered by the system.

According to a seventh aspect of the present invention there is provideda drug delivery device (210) comprising:

-   i) a housing (212);-   ii) a means (214) for generating a force capable of pushing a drug    (216) from a packaging (218) into a human or animal body;-   iii) a means (220) for transmitting said force to push the drug    (216) from the packaging (218) into the human or animal body; and-   iv) a means (238, 242 b) for triggering the device.

The numbers are again included for illustrative purposes and are not tobe construed as limiting.

Such a device can be a reusable device which further comprises a means(222) for receiving a packaged drug (2100); and a means (224) forpriming the device.

Alternatively the device can be a single use device in which case thepackaged drug (2100) will be an integral part of the device. Such adevice can be provided in a pre primed form which just needs triggeringor in a form requiring it to be primed.

A device according to the invention has a number of advantages comparedto current needle free devices.

It comprises a small number of components and is therefore cheap tomanufacture and assemble. It is also relatively small (currently thesame size as a dry marker pen).

In a preferred embodiment of the device, it can only be actuated byinserting a packaged drug and pushing the skin tensioning end of thepackaged drug against a solid object. The priming and actuation of thedevice by pushing the end of the device against the skin ensures thatthere is a reliable and consistent contact and tensioning of the skin ondelivery of the drug. Additionally, by setting the device such that theforce required to actuate it is from, for example, 20-30 Newton theforce will be too high for a patient to accidentally actuate the devicewithout pushing it firmly against the body's tensioned skin, therebyproviding a significant safety feature.

A spring and cap arrangement makes it is possible to adjust theactuation force by altering the tension on the spring. By screwing thecap further onto the upper barrel the spring is tensioned and byunscrewing it the force can be reduced. Alternatively, instead of a coilspring as the main power source, the device could incorporate any othertype of mechanical spring or a gas spring. In an alternative embodimentthe spring could be pre-tensioned during manufacture to avoid having totension the spring during the drug administration. This would result ina single use device in which case the packaged drug would most likely bean integral part of the device.

The velocity of the impact hammer during administration of thetherapeutic agent is less than 20 m/s, more preferably less than 10 m/s,more preferably still less than 5 m/s and most preferably in the orderof 0.1-2 m/s. The skilled man will appreciate that the actual speed mayvary with the mass of the impact hammer and thus the impact imparted onthe delivery dose. As a consequence the therapeutic agent is deliveredby a pushing action from the end of the packaged drug rather than by afiring action (as would be the case with a bullet leaving the barrel ofa gun).

To ensure that the device actuates automatically when the correct forceis applied the hammer has a shaped shoulder region which engages acorrespondingly shaped surface in a wall separating the upper and lowerbarrels. The device will actuate only when the substantiallyfrustoconical sections fully engage. This will be at the same mainspring tension every administration and if the administration is abortedbefore the frustoconical sections engage then the packaged drug can beremoved safely without leaving the device primed.

In a preferred embodiment the device can't be primed until the packageddrug is attached thereto since it is the packaged drug that acts againstthe piston in the device to cause the spring to be tensioned. This makesthe device particularly safe. It also means it can't be actuated whennot loaded such that an operator can't use the device in a belief theyare providing an injection.

In the case of a reusable device a stewing spring returns the impacthammer into it's non axially aligned position at the end of eachadministration.

Furthermore, because the reusable components of the system (allcomponents except those of the packaged drug) do not come into contactwith the target tissue for the drug administration they do need to besterile.

All components apart from the springs can be moulded making the devicecheap to manufacture and the limited number of parts and their ease ofassembly keeps assembling costs to a minimum.

A range of custom packaged drugs will fit the delivery device butpatients will not be able to easily introduce their own therapeuticcompounds into the drug cassettes (as can be done with a needle andsyringe).

The device is suitable for both human and veterinary applications.

The device is particularly suitable for self administration of drugs andrequires minimal training.

According to an eighth and related aspect of the invention there isprovided a packaged drug (2100), for use with a drug delivery device,comprising a packaging (218) containing a drug (216), said packaging(218) comprising a housing (218 a, 218 b) having a channel (2106)running there through and in which is disposed a drive pin or otherelement (2108), a skin piercing means (2110; 2112), and the drug (216),said housing (218 a, 218 b) comprising

-   -   i) a region (2102) allowing the packaged drug (2100) to be        slidably mounted to the drug delivery device (210); and    -   ii) an end (2104) adapted to engage and tension the skin.

In the case of a drug splinter the skin piercing means and the drug maybe one of the same.

Preferably the drug is disposed between the drive pin and the skinpiercing means.

Preferably the packaged drug takes the form of a disposable end cap,cartridge, cassette or carousel, containing a single or multiple dosesof the drug.

Preferably the region for engaging the packaged drug to the drugdelivery device in a slidable manner additionally comprises a means forpositively locking it to the device such that it can still slide withinthe device but will not fall out under gravity. Such a means might be asprung pin or spigot which exerts a frictional force against the deviceor a mechanism whereby the packaged drug is inserted in a particularorientation and turned so that it is precluded from being removed unlessit is turned back into the position in which it was allowed to enter.

In a first embodiment the packaged drug houses either a pioneerprojectile in combination with a drug in a contained state, morepreferably a solid, or a drug splinter (a single solid entity).

In a second embodiment the piercing means comprises a needle with twosharp ends, one for puncturing the skin and the other for puncturing amembrane of a receptacle containing the drug, the drug being releasedinto the needle from where it drains out into the body through theneedle. The drug is preferably a liquid and is contained in thereceptacle which is disposed in the channel. Advantageous features ofthe device include a spacer between the membrane piercing end of theneedle and the membrane of the drug containing receptacle to prevent theneedle coming into contact with the membrane prior to actuation. Thespacer is either resilient or compressible and may be supported by aplate attached to the needle. The receptacle is preferably sealed by thedrive pin or other like element.

In a third embodiment the packaged drug may contain a drug in any state(e.g. solid, semi solid or liquid), the actuation of the device causing,in a two step operation, first the entry of a pioneer projectile andonly then the release of the drug from a thin walled tube. Release ofthe drug may optionally require the breaking of a membrane supportingthe drug in the tube.

In a variation of this embodiment the pioneer projectile, which islocated immediately in front of the thin tube, could be replaced by aretractable needle tip which is, or is integral with, the thin walledtube. As per embodiment 1 and 2 described above, the thin walled tubecould have a compression spring or other resilient member associatedtherewith to withdraw the thin walled tube following the injection.

A particularly clever feature of this embodiment is the form of thedrive pin or element which has a plurality of flexible or frangiblearms, in the embodiment illustrated two, extending from its main body.These arms extend outwards (splay) when they ride over a ramped surfaceprovided on the housing, are forced away from the body, and ride over alip on the tube as a consequence of the flex or frangibility. Inconsequence the body of the drive pin or element can move down the tube.This arrangement facilitates a two step operation whereby in a firststep the drive pin or element acts on the tube causing it to move andpush the pioneer projectile into the skin, and then, and only when thefirst step is complete, the arms are caused to splay and/or snap therebyallowing the drive pin body to push the drug contents from the tube. Inthe case where the arms are frangible the arms will snap off as a resultof an area of weakness formed about the shoulder region and fall into acavity about the ramped region. A frangible system has two advantages:firstly it should ensure full injection occurs, and secondly it willmean the packaged drug can't be re-used. The ramp is preferably“circular” in design, taking the form of a frustoconical surface. Thishas the advantage that it can be easily moulded and does not require thearms to be orientated for contact.

Depending on the diameter of the thin walled tube and the viscosity ofthe therapeutic compound, the thin walled tube may need to be sealed, orpartially sealed to avoid premature loss of the drug. However the actionof the drive pin body will be sufficient to break any seal allowing thedrug to be released and pushed into the patient.

An advantage of the packaged drugs exemplified is their small cheapsub-assembly. They are also easy to handle and place into the deviceprior to administration. Their size also facilitates easy storage in,for example, refrigerators.

The packaged drug may be sealed in a foil pouch or the like to preventingress of, for example, moisture, oxygen, light, bacteria or other drugdegrading or contaminating agents.

In those embodiments having a pioneer projectile the tip will, in mostinstances, be positioned a few millimetres from the end of the drugcassette so that it is moving when it strikes the target tissue.

Preferably the end adapted to engage and tension the skin comprises oneor more projections about the channel exit, most preferably in the formof an annular ring, as such an arrangement most effectively tensions theskin.

A retention system may advantageously be employed to hold the drug andpioneer projectile in place in the channel. This might be achieved by,for example, extruding or moulding the drug and/or pioneer projectilewith a number of small splines or other features along their outersurface. These splines or other features would provide a frictional fitbut would not prohibit the drug from being administered. Alternatively,the channel of the packaging might have a small feature, such as, forexample, a retaining bump or other projection over which the pioneerprojectile and drug have to be pushed.

A tamper or use evident seal or other indicator means may additionallybe placed over the top end of the packaged drug so that when e.g. theseal is broken it is obvious that the packaged drug has not beeninterfered with and/or is spent.

Additionally or alternatively a seal may be place over the exit of thechannel of the packaged drug. It would be preferable to remove this sealprior to administration of the drug but it would best be designed suchthat the administration could be carried out through the seal just incase it wasn't removed by the user.

According to yet a further aspect of the invention there is provided amethod of delivering a drug to a human or animal using a device and/orpackaged drug according to the invention.

The various aspects of the invention will now be described, by way ofexample only, with reference to the following Figures and Examples.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a-e are embodiments of pioneer projectiles of varying shapes andsizes;

FIG. 2 a-c are embodiments of pioneer projectiles with hollow drivenfaces;

FIG. 3 a-d are embodiments of pioneer projectiles with an obliquecutting edge;

FIG. 4 a-c are embodiments of pioneer projectiles with an obliquecutting edge and hollow driven faces;

FIG. 5 a-c are a plan view, side elevation and end elevationrespectively of a pioneer projectile with an oblique cutting edge;

FIG. 6 a-c are a plan view, side elevation and end elevationrespectively of a pioneer projectile with a central piercing point andfaceted sides;

FIG. 7 a-c are a plan view, side elevation and end elevationrespectively of a pioneer projectile with a central cutting edge;

FIG. 8 a-c are a plan view, side elevation and end elevationrespectively of a pioneer projectile with a central piercing point;

FIG. 9 is one embodiment of an injectate of the invention shown housedin a support or device chamber;

FIG. 10 is another embodiment of an injectate of the invention shownhoused in a support or device chamber;

FIG. 11 is another embodiment of an injectate of the invention shownhoused in a support or device chamber;

FIG. 12 is another embodiment of an injectate of the invention shownhoused in a support or device chamber;

FIG. 13 is another embodiment of an injectate of the invention shownhoused in a support or device chamber;

FIG. 14 is another embodiment of an injectate of the invention shownhoused in a support or device chamber;

FIG. 15 is another embodiment of an injectate of the invention shownhoused in a support or device chamber;

FIG. 16 is cross sectional view of a delivery device of the invention;

FIG. 17 is one embodiment of a reusable device according to one aspectof the invention with one embodiment of a packaged drug according toanother aspect attached thereto, the device being shown pre-use;

FIGS. 18 a, b, and c illustrate a device substantially similar to thedevice illustrated in FIG. 17 in:

a) its assembled form

b) at the point where it is fully primed and about to self actuate; and

c) in its post actuation position;

FIG. 19 is a packaged drug according to one aspect of the invention inwhich the drug is in a solid or otherwise contained form and follows apioneer projectile;

FIG. 20 is a packaged drug according to another aspect of the inventionin which the drug is in a liquid form and is released and injected via aretractable needle; and

FIG. 21 is a packaged drug according to yet a further aspect of theinvention in which the packaging is adapted to hold a drug in a solid orliquid form and in which the end of the packaging is modified to beparticularly well adapted to skin tensioning.

DETAILED DESCRIPTION

Referring to the drawings, FIG. 1 a is a side elevation of a pioneerprojectile 10 according to one aspect of the present invention. It ismade of a crystalline or amorphous material, preferably a glassymaterial, (e.g. a sugar glass such as trehalose, palatinit,glucopyranosyl sorbitol, glucopyranosyl mannitol, lactitol ormonosaccharide alcohols such as mannitol or inositol) which iswater-soluble and dissolves in the body. The material may include ahardening agent, such as, for example, povidone (pvp). The pioneerprojectile comprises a penetrating face 12 comprising one of morefacets, which has a central point, one or more guiding faces 16 forguiding the pioneer projectile within a central aperture or chamber of aneedleless device for injecting an injectate (comprising the pioneerprojectile and a formulation) thus ensuring the pioneer projectile meetsthe skin at a suitable angle to aid penetration, and a driven face 14.The pioneer projectile has an aspect ratio (width W to height H) ofabout 1.25:1.

The pioneer projectile can however take a number of forms and somefurther embodiments are illustrated in FIG. 1 b-d, FIG. 2 a-2 c, FIG. 3a-d, FIG. 4 a-c, FIG. 5 a-c, FIG. 6 a-c; FIG. 7 a-c and FIG. 8 a-c.

Briefly: FIG. 1 b illustrates a pioneer projectile with a very smallaspect ratio of about 1:0.5; FIG. 1 c illustrates a pioneer projectilewith an aspect ratio of about 1:2; FIG. 1 d illustrates a pioneerprojectile with a blunt and planar penetrating face 12, and an aspectratio of about 1:0.2; and FIG. 1 e illustrates a pioneer projectilewhich does not have a guiding face 16 but consists of a penetrating face12 and a driven face 14.

FIGS. 2 a to 2 c illustrate variations in the driven face 14. Thus inFIG. 2 a the driven face is completely hollowed forming a void 18 whichcan hold, at least in part, at least one therapeutic compound orcompound containing formulation. In FIG. 2 b the hollow 18 has a flatbottom 20 and in FIG. 2 c it has a concave bottom 22.

Of course, the penetrating face 12 need not have a central point andFIGS. 3 a-d, and 4 a-c illustrate embodiments in which the pioneerprojectiles have an oblique cutting edge 24.

The shape of the penetrating face can, as noted above, take a number offorms as exemplified with reference to FIGS. 5-8. In each of these Figsa) is a plan view; b) is a side elevation and c) is an end elevation.Thus:

In FIG. 5 the pioneer projectile is circular in x-section (FIG. 5 a),has an oblique cutting edge 24 (FIG. 5 b), and a planar penetrating face12 (FIG. 5 c).

In FIG. 6 the pioneer projectile is circular in x-section (FIG. 6 a),has a central point 26 (FIG. 6 b), and four facets 28 making up thepenetrating face 12 (FIG. 6 c).

In FIG. 7 the pioneer projectile is circular in x-section (FIG. 7 a),has a central cutting edge 30 (FIG. 7 b), and two facets 28 making upthe penetrating face 12 (FIG. 7 c).

In FIG. 8 the pioneer projectile is circular in x-section (FIG. 8 a),has a conical penetrating face (FIG. 8 b), culminating in a point 30 anda penetrating face 12 (FIG. 8 c).

Of course the pioneer projectile need not be circular in cross sectionbut could be, for example, three sided (triangular), four sided (square)or indeed any other suitable shape.

A pioneer projectile might be manufactured in a number of ways such asby moulding, extrusion or sectioning a rod of the material.

Preferably the pioneer projectile will dissolve in the tissue in amatter of minutes or hours depending on the material used.

The pioneer projectile together with at least one therapeutic compoundor formulation forms an injectate.

The physical characteristics of the formulation are very important toensure that the injectate can be administered to the skin in a reliableand repeatable manner

The formulation could take a number of forms:

In one embodiment it might take the form of a paste. This can beachieved by mixing the active drug with the appropriate excipients toend up with consistency, say, like toothpaste. The excipients wouldobviously need to maintain the active ingredient in a condition suchthat it was still active during manufacture, storage and administration.

In other embodiments the formulation will be a semi solid, gel, solid orcontained liquid.

The therapeutic component of the formulation might be present in one ormore of the following formats:

1. Pure drug;

2. With excipients to alter the physical characteristic of the material;

3. With excipients to bulk out the active ingredient;

4. With excipients to buffer the active ingredient;

5. With excipients to change the release profile of the activeingredient; and

6. As a mixture of more than one therapeutic compound.

The formulation can be designed to give the desired release profile forthe application. This might involve either a sustained releaseformulation or a quick dissolving formulation for immediate release intothe body. In some cases, such as for the administration of insulin, aformulation might be required that provides an immediate release of someof the therapeutic compound and then a sustained release of anothercomponent in the formulation. This might for example be achieved byhaving the formulation in a plurality of parts or by incorporating amedicament into the pioneer projectile.

Alternatively the therapeutic compound might be formulated as smallbeads. A number of the beads could be lined up in the device behind apioneer projectile. On actuation of the device the pioneer projectilepierces the skin and the beads are pushed into the skin behind thepioneer projectile.

The therapeutic component of the formulation must of course not reactwith the material used for the pioneer projectile or the materials usedin the delivery system.

FIGS. 9 to 15 are some embodiments illustrating injectates andformulations of the invention.

In FIG. 9 an injectate 40 comprises a pioneer projectile 10 and aformulation 42. The formulation is in a contained state supported by itsown viscosity or a membrane 44. The formulation is thus a containedliquid or a solid. The injectate may be self-supporting or contained inan optional support 46 which may be a chamber 76 of a device or athrowaway component.

In FIG. 10 the formulation is a high viscosity liquid, gel, paste orsemi-solid.

FIG. 11 illustrates an injectate comprising a plurality of differentformulations 42 a, 42 b and 42 c. These could be formulations withdifferent release profiles or different active ingredients, for examplecombination therapies. Though not illustrated there could be membranesbetween the components e.g. lipid soluble membranes betweenwater-soluble formulations and or an end piece.

FIGS. 12, 13 and 14 illustrate injectates with different solidformulations. In FIG. 12 the solid formulation takes the form of beads46. In FIGS. 13 and 14 they are granules, particles or crystals 48.

In FIG. 15 a barrier 50 is shown between the formulation 42 and thepioneer projectile 10.

The skilled man will of course realise that the features illustratedwith reference to one embodiment could easily be applied to otherembodiments.

An injectate will be introduced into a human or animal using a devicethat injects the injectate in a needleless manner.

One such device is illustrated by way of example only in FIG. 16.

The needleless injection device 60 is shown in the primed position. Itcomprises an outer housing or holder 62 the lowermost end 64 of which isslidably mounted over the uppermost end 66 of an innermost casing 68.

At the lowermost end 70 of innermost casing 68 is fitted a disposablecomponent 72 such as, for example, a drug cassette. The disposablecomponent comprises a casing 74 having a central aperture or chamber 76in which is mounted the injectate 40 comprising the pioneer projectile10 and the formulate 42. A large headed ejector pin 78 comprising a flathead 80 and an elongate body 82 is positioned over the injectate 40 sothat when the ejector pin is contacted, in use, by a striker 84 it ispushed along the aperture or chamber 76 and out into the patient. Aresilient member 87, such as a rubber block urges the ejector pin back alittle after injection.

The disposable component 72 is loaded into the needleless injectiondevice, by for example, screwing it into the lowermost end 70 of theinner housing 68.

Mounted within the innermost housing 68 is a striker guide 86 having asurface 88 which maintains a detent 90 in the loaded position (shown)and houses an actuating mechanism or spring 92 and spring follower 94.

The disposable component 72 is shaped such that when it is in contactwith the skin it pre-tensions it prior to actuation. This ensures thatthe dosage will penetrate the skin rather than just stretch the skin.

The injector pin 78 is designed to push the injectate beyond the end ofthe device by up to (say) 2.5 mm. This means that the end of theinjector pin (which preferably has the same profile and diameter as theend of the pioneer projectile) might just penetrate the skin but itwould ensure that the injectate has been fully administered into theskin.

Prior to actuation, the tip of the injectate might be in contact withthe skin. However, it is preferred that the tip is a few millimetresaway from the skin prior to actuation. This ensures that the injectateis moving when it impacts the skin and also ensures that the tip of theinjectate does not start to dissolve, and therefore soften the tip, withany moisture from the skin surface when the device is placed on theskin.

To use the device 60 the outer most casing is retracted (pulled in thedirection of arrow A) so that it slides against the innermost housing68. This action causes the spring 92 to be compressed, and the detent tobe moved from a vertical position to the position shown where it is heldstable against surface 88. In the process a quill spring 96 stabilisesthe detent by abutting against a surface 98. Once loaded the disposablecomponent, is screwed into the end 70 of the innermost housing 68 of thedevice 60.

The injector pin 78 that pushes the injectate into the skin ispreferably, (but not necessarily) in contact with the injectate prior toactuation.

To actuate the device a user, for example, grips the device around theouter housing 62 with their thumb over the end cap 102. The end face 100of the disposable component 72 is positioned against a patient's skin,which should be held taught, and the outer housing 62 is pushed in adirection away from arrow A. This action causes the outermost casing toslide over the inner housing 68. As it does so the detent is caused torotate about it's axle 104 as a result of the detent riding up inclinedwall 106. This forces the quill spring 96 out (as shown by the brokenline). When the detent reaches a vertical position the coil springreleases its stored energy and assists in ensuring the striker 84travels along the striker guide 86 until it contacts the head 80 of theejector pin 78 with a force that causes the injectate 40 to pierce theskin. The ejector pin 78 continues to push the formulation 42 into thepatient to the required depth, which is determined by the length of theinjectate and the extent to which it is pushed by the ejector pin 78.The rubber stop 87 is squashed by the ejector pin head 80 duringdelivery of the injectate but the elastic properties of the rubber stop87 enable the tip of the ejector pin to be withdrawn into the disposablecomponent 72 of the device.

Injection Sites

The injectate could potentially be injected in a wide number of sitesacross the human or animal body. The easiest direction to administer theinjectate is perpendicular to the skin and so with most skin sites thiswould mean penetrating the epidermis into the dermis and, depending onthe skin thickness, into the subcutaneous layers or muscle. The ‘best’injection sites might therefore be those where there is the smallestdensity of nerve endings to avoid any pain that might be associated withthe injection. This might include injections to the back or to the lobeof the ear.

Alternatively, injection sites might include those with a thickerepidermis so that the injectate does not penetrate into the dermis wherethe nerve endings are located. The injectate might be injected obliquelyinto the skin so that it is located totally in the epidermis. The sameresult might be achieved by injection into a fold of skin that has beenpinched.

The elastic properties of the skin can be employed to seal the skinafter the injectate has been administered, as is often the case withsplinters. This ensures the drug does not leak from the skin as itdissolves.

The most likely area of the body for drug administration with thistechnology is the stomach because of the high fat content and easyaccessibility for self-administration. An alternative might be the thighalthough this is often less accessible if the recipient is wearingtrousers.

Product Applications

There are many possible product applications for this technology becauseof the doses that are achievable including therapeutic, prophylactic anddiagnostic applications. Illustrative examples include, but are notlimited to:

Conventional Vaccines—first and third world applications or veterinaryapplications;

Insulin;

Migraine Treatments; and

Hormones.

The term “at least one therapeutic compound or a formulation containingat least one therapeutic compound” as used in this application isintended to cover prophylactic and diagnostic applications as well astherapeutic applications.

The maximum dose that could be delivered using the technique will dependupon a number of factors. However, an injectate with an overall lengthof approximately 4.0 mm and a diameter of approximately 1.0 mm (similarto a 19G venflon) would be sufficient to allow a dose of approximately 2mg of a standard therapeutic in one administration. This magnitude ofdose would be suitable for each of the applications exemplified above.If several doses of injectate are delivered simultaneously then there isthe potential for an even larger number of applications.

Delivery of the injectate will be very quick and any pain associatedwith the delivery technique should not be any worse than a needle ofsimilar dimensions. If the delivery technique were painful then it wouldbe possible to anaesthetise the tissue prior to the injection. To avoidneedles then this anaesthetic might be given with a patch, a spray or acream.

The device illustrated in FIG. 17 is a (reusable) drug delivery device(210), with a packaged drug (2100) fitted thereto. It comprises very fewcomponents. They include

i) a housing (212);

ii) a means (214) for generating a force capable of pushing a drug (216)from a packaging (218) into a human or animal body;

iii) a means (220) for transmitting said force to push the drug (216)from the packaging (218) into the human or animal body;

iv) a means (222) for receiving a packaged drug (2100);

v) a means (224) for priming the device; and

vi) a means (238,242 b) for triggering the device.

In the embodiment shown the device is primed and triggered in a singleaction.

The delivery device (210) which may be absent of the packaged drug(2100) is spring powered. It can deliver the drug or a formulationcontaining a therapeutic compound (hereafter drug) in a solid,semi-solid or liquid form. By altering the form of the packaged drug(2100) the device can be used to either deliver drugs through aretractable needle (FIG. 20), or behind a “pioneer projectile” (FIGS. 19and 21). It can also be used to deliver a solid drug splinter.

Looking at the device in more detail it comprises a number of componentswhich are readily assembled and easily sterilised making manufacturecheap.

The body of the device comprises a three part housing (212) comprising afirst housing component (212 a) defining an upper barrel (228) whichhouses the force generating means (214), a second housing component (212b) defining a lower barrel (230) which houses the packaged drug (2100)and the means (220) for transmitting the force to push the drug (216)from its packaging (218). The first and second housing components (212a; 212 b) connect to one another, and a third housing component (212 c),which preferably takes the form of a screw cap (232), fits over the endof the first housing component to close off the upper barrel (228).

Within the upper barrel (228) is fitted the means (214) for generatingthe force capable of pushing the drug (216) from its packaging. In theembodiment shown this takes the form of a mechanical coil spring whichcan generate a force of from about 10-40 N, more preferably 15-35 N andmost preferably 18-31 N. The spring is connected at its lower end to aspring follower (236) which is slidably mounted in the upper barrel(228). Above the spring is a compression bar (234) which provides acontact surface against which the spring can act. By screwing orunscrewing the cap (232) from the housing component (212 a) the springcan be caused to compress or relax thereby providing a means foradjusting the force that can be generated by it. In FIG. 17 the springis shown at minimum pre-load.

The upper barrel (228) and lower barrel (230) are separated from oneanother by a wall (242) with a communicating aperture (243) therein andit is on the upper surface (242 a) of this wall that the spring follower(236) sits. The means (220) for transmitting the force generated by thespring takes the form of an impact hammer one end (220 a) of whichpasses through the communicating aperture (243) where it contacts springfollower (236). In use the uppermost end (220 a) of the impact hammerslides through the communicating aperture (243) pushing the springfollower (236) up the upper barrel (228) causing the spring to becompressed thus priming the device.

Within the lower barrel is housed not only the majority of the impacthammer (220), but a slewing spring (244) and a sliding piston (248)having an aperture (246) therein, such that the lower barrel canoperatively communicate with the packaged drug (2100) which is securedto the device via the receiving means (222) provided at the deviceslowermost end (249).

The slewing spring functions to draw the longitudinal axis of the impacthammer off centre (FIG. 18 a) in the devices rest position. However, thehammer is adapted by way of a shaped shoulder region (238), (which in apreferred embodiment is substantially frustoconical, as illustrated) tobe drawn into axial alignment with the aperture (246) in the slidingpiston, against the action of the slewing spring (244), such that whenit is fully primed the device automatically actuates. Accordingly thelowermost surface (242 b) of the wall (242) is shaped to receive theshaped shoulder region (238) of the impact hammer and cause the impacthammer to be axially aligned with the aperture (246) in the slidingpiston (248) such that it is driven by the spring (214) through theaperture (246) in the sliding piston (248) where it contacts a drive pin(2108) or other element causing the drug (216) to be pushed out of itspackaging (218) into the human or animal. In contrast with the FIG. 17embodiment it should also be noted that the end (220 a) of the impacthammer graduates to a point (being substantially conical) and is seatedin a similarly shaped recess (236 a) in the spring follower (236). Theshaping of the hammer end (220 a) and the provision of the similarlyshaped recess (236 a) in the spring follower (236) further improvesreliability of actuation.

By comparison of FIG. 18 a with FIGS. 18 b and c it will be apparentthat once a packaged drug (2100) has been attached to the lower most end(249) of the device (210) it can be actuated by a user holding thedevice about it's housing (212) and pressing the device (210) firmlyagainst the patients skin. This causes first the skin to be tensionedand then the packaged drug (2100) slides up the lower chamber (230)pushing the piston (248) which in turn pushes the impact hammer (220).As it does so the upper end (220 a) of the impact hammer pushes againstthe spring follower (236) causing the spring (214) to be compresseduntil the necessary drive force is reached. This is at the pointillustrated in FIG. 18 b. At this point the shaped shoulder region.(238) is drawn into the shaped lowermost surface (242 b) of wall (242),the action of the slewing spring (244) is countered, the spring (214) isfully charged and the impact hammer (220) axially aligned with theaperture (246) in the sliding piston (248) such that it willautomatically actuate, the spring (214) forcing the impact hammer (220)through the aperture (246) in the piston (248) causing it to push thedrive pin (2108) which in turn, depending on the mechanism employed inthe packaged drug (2100) (see FIGS. 19 to 21) causes the drug to bedispensed into the human or animal. Significantly the longitudinal axisof the impact hammer can't be aligned with the aperture (246) in thesliding piston (248) until it reaches the set actuating force which isset to coincide with the point at which the shaped shoulder region (238)contacts the shaped lowermost surface (242 b) of wall (242) thusproviding a safety mechanism against accidental actuation. When itreaches this point triggering is automatic and the device is actuated(FIG. 18 c).

It should be noted that on actuation the hammer moves only a shortdistance, less than 10 mm, more preferably less than 5 mm and typicallyabout 3 mm before impacting the drive pin and therefore moves (say)approx 5 mm before the pioneer projectile strikes the skin. This meansthat the maximum force and impact are all in the first few millimetresof travel, when the maximum force is required to pierce the skin.Through the rest of the delivery, the force is reducing as the mainspring power is diminishing and also the slewing spring is beingcompressed (FIG. 18 c). This means that the force tapers off during thesecond half of the delivery when less force is required.

Therefore the force profile through the whole delivery matches therequirements i.e. a high force and impact to pierce the skin and then areduced force to push the injectate into the skin.

In the case of a reusable device the packaged drug is removed from thedevice and discarded. The slewing spring will assist in this action. Asthe packaged drug (2100) is removed from the device the slewing spring(244) acts to draw the impact hammer (220) so that it is not axiallyaligned with the aperture (246) in the piston (248) and the device (210)is ready to receive a new packaged drug.

Such a device can be used to dispense a drug in a variety of differentforms depending on how it is packaged.

To demonstrate the versatility of the device three different designs(FIGS. 19, 20, and 21) of packaged drug (2100) are illustrated assuitable for use with the device. All three embodiments illustrate thedispensing of a single dose but the skilled man will appreciate thatmulti-doses could also be dispensed simultaneously or sequentially withthe device of the invention. Similarly, the device could be produced ina pre-primed form with the packaged drug forming an integral part of thedevice.

Referring to FIG. 19, in one embodiment the packaged drug (2100) takesthe form of an end piece which is adapted to be slidably mountable inthe device (210). The packaging (218) takes the form of a two-piecehousing (218 a, 218 b), thereby simplifying construction and assembly. Afirst housing element (218 a) is the shape of a hollow inverted “T” andcomprises a region (2102) (the stem of the “T”) which serves in use toslidably engage the device (210) allowing the packaged drug to slide upthe lower chamber (230) of the device (210), and a “cross piece” againstwhich the second element (218 b) abuts. A central channel (2106 a) runsthrough the middle of the stem exiting at the crosspiece. The secondelement (218 b) comprises an end (2104) which is shaped to tension theskin. The second element (218 b) is also substantially the shape of aninverted T and has a channel (2106 b) running down the centre axis ofthe inverted T. The respective channels (2106 a, 2106 b) communicatewith one another to form a single channel (2106) which runs rightthrough the packaging (218). The channel (2106 b) houses a pioneerprojectile (2110) and the drug (216) or a drug splinter (effectively2110, 216), the skin contacting end of which is set a few millimetres infrom the skin tensioning surface of the device to ensure it is moving atthe requisite speed when it contacts the skin. It also houses the lowerend (2108 b) of the drive pin (2108). At the end remote from the skintensioning surface the channel (2106 b) opens out to house a resilientmember e.g. a spring (2114). The placing of a resilient member under thehead (2108 a) of the drive pin allows the drive pin to be withdrawn backinto the housing immediately after actuation. The drive pin (2108) isslidably mounted in the channel (2106) so that when the head isdepressed by the hammer of the device the drive pin moves down thechannel pushing the pioneer projectile and drug (2110, 2216) from thechannel (106 b) into the human or animal body. The pioneer projectile(2110) and drug (216) are held in place in the channel (2106 b) by, forexample, a breakable membrane (not shown) or appropriate frictionalmeans e.g. one or more markings or splines on either the pioneerprojectile, drug and or channel (2106 b) surface.

The packaged drug illustrated in FIG. 19 is suitable for the injectionof a “contained” drug behind a pioneer projectile which can penetratethe skin and create a channel into which the drug is pushed asdescribed. This type of packaged drug is also suitable for theadministration of drug splinters or rods of a solid therapeutic compoundwhich have a sharp tip as per WO 94/22423. The therapeutic compound ortherapeutic compound and tip are initially located in the channel (2106)of the packaging (218). The distal end (2108 b) of the drive pin may ormay not be in contact with the uppermost end of the therapeutic compoundprior to actuation. When the drive pin head (2108 a) is struck by theimpact hammer the drive pin (2108) pushes the therapeutic compound (andpioneer projectile, if included) into the target tissue.

The end of the drive pin may just penetrate the outer layers of the skinto ensure that the therapeutic compound is completely delivered into theskin. Alternatively, the packaged drug may include a short rod (or rods)of a placebo or pharmaceutical compound between the end of the drive pinand the therapeutic compound, which can be used to push the therapeuticcompound fully into the skin. In this case it would not matter if theplacebo rods entered the skin but it would ensure that the drive pin didnot have to penetrate the skin. The benefits of this are that the drivepin would not be left protruding from the packaged drug following theadministration and would not be contaminated with bodily fluids and itwould therefore not pose a health risk in terms of disposal. Analternative is to include a piece of rubber or foam, or as illustrated alight spring (2114), under the head (2108 a) of the drive pin to ensurethat the tip of the drive pin is withdrawn into the spent packagingafter administration.

FIG. 20 illustrates an alternative design of a packaged drug for usewith a device according to the invention. The packaged drug comprises atwo piece housing (218 a, 218 b) which is identical to that of the FIG.19 embodiment. This simplifies manufacture as the housing components canbe used for a packaged drug which is solid (as per the FIG. 19embodiment) or one which is liquid. In order to be adapted to dispense aliquid a needle (2112) sits in the channel (2106), it's lower end (2112b) being in the channel (2106 b) of housing component (218 b) and itsupper end (2112 a) extending into the channel (2106 a) of housingcomponent (218 b). The needle (2112) is obliquely cut at both ends toprovide sharp points. Attached to the upper end (2112 a) of the needleis a support plate (2113) on which is seated a resilient or compressiblespacer (2126) which extends above the tip of the upper end (2112 a) ofthe needle. Seated on the spacer (2126) immediately above the tip of theneedle (2112) is a liquid drug containing receptacle (2120). Thereceptacle comprises one or more side walls (2121) and a puncturablebase (2122) which together define a receptacle cavity which is filledwith the drug (216) through an opening (2124). The receptacle is sealedby a drive pin or element (2108) which sits in the receptacle opening(2124).

In use the hammer of the drug delivery device contacts the drive elementhead (2108 a) causing the receptacle to be pushed down the channel (2106a) of the housing element (218 a). The spacer (2126) is compressedcausing the needle to puncture the base (2122). Consequently the needle(2112) is filled by some of the drug contents (216) of the receptaclethereby expelling air from the needle prior to piercing of the skin anddelivery of the drug. The force exerted on the support plate (2113)forces the needle into the skin where the liquid drug contents (216)drain into the human or animal through the tract formed by the needle(2112). As the user of the device removes the device from the skin, thedrug package is pushed substantially out of the end of the device by theaction of the slewing spring, and the needle is withdrawn into the drugpackage by the action of the spring (2114).

In yet a further embodiment, and as illustrated in FIG. 21 there is apackaged drug (2100) which is adapted to hold a drug (216) in any state,liquid, semi solid or solid. As in the previous embodiments the housing(218) preferably takes the form of a two piece housing (218 a, 218 b)although in this case the housing elements are shaped differently. Inchannel (2106 b) of the second housing element (218 b) is housed apioneer projectile (2110) and the lowermost part of a drug containingreceptacle (2120) in the form of a thin walled metal tube which issealed with a breakable membrane (2122). The tube terminates at it'suppermost end in a lip (2121) on which rest a pair of flexible arms(2128) of a drive element (2108). The receptacle is sealed by the driveelement (2108). At the end remote from the skin tensioning surface ofthe second housing element (218 b) is a ramped surface (2130). Theuppermost part of the drug containing receptacle (2120) and the driveelement (2108) sit in a cavity between the housing elements (218 a, 218b) and which can be considered an extension of channel (2106 a) formedin the first housing element (218 a). The end (2104) in this embodimentis particularly well suited to skin tensioning and includes an annularring (2105) located immediately about the channel (2106) exit. Theannular ring in this embodiment is about 3 mm in diameter (including thechannel which is about 1 mm in diameter) and depth. By way of comparisonthe end (2104) has a diameter of about 16 mm. The depth and width neednot be 3 mm by 3 mm but should generally be in the range 1.5 mm to 6 mm.Any more than this and it may cause pain and bruising and any less thanthis and it may not adequately tension the skin. This annular ring whichmay be a whole ring or a broken ring comprising a number of projectingelements disposed in a substantially annular fashion about the channelexit could be a feature of any embodiment. To simplify construction inthis embodiment the drive pin head (2108 a) is produced as separatecomponent to the lower and elongate end (2108 b) of the drive pin.

In use the hammer of the drug delivery device contacts the drive elementhead (2108 a) causing the receptacle to be pushed down the channel (2106b) as a consequence of the force exerted by the flexible arms (2128) ofthe drive element (2108) against the lip (2121) of the receptacle(2120). This causes the pioneer projectile (2110) to be pushed into thepatient. Once the pioneer projectile has entered the patient theflexible arms (2128) of the drive element (2108) contact the rampsurface (2130) of the second housing element (218 b) and are caused toflex apart and ride over the lip (2121) and/or snap. As a consequencethe lower part (2108 b) of the drive element is able to move down thereceptacle (2120) pushing the drug (216) contents out into a tractformed by the pioneer projectile (2110). Preferably the end of thereceptacle which takes the form of a thin walled tube just enters theskin before the drug is delivered. This ensures that if a liquid drug isused the drug follows the pioneer projectile into the skin rather thanescaping along the skin surface.

The main advantage of the FIG. 21 embodiment is for the injection ofliquids as it ensures that the liquid is contained during theadministration and is guided by the thin walled metal tube into thetarget tissue. However, the drug contents need not be restricted toliquids.

A feature of the device illustrated which further distinguishes it fromother hand powered systems is that the force generated by the spring isthe delivery force and there is substantially no additional forcegenerated by the operator due to the gradual priming and instantaneousactuation when the device reaches the delivery force set.

In contrast devices which include a break tab or other snap means toactuate the device can't have the force carefully controlled and as aconsequence the greater the force exerted by the user the greater thevelocity of impact by the drug with the skin.

With the system detailed in this application the hand force compressesthe main spring to a preset point at which the drug package is insertedto virtually its maximum point within the device. At this point theactuation takes place and the predetermined spring strength delivers thedrug. Any extra force by the hand is dissipated over the whole of thearea of the end of the device.

An alternative way of viewing this is to consider the skin as a sponge.In devices utilising snap tabs, when the snap tabs are broken all theforce by the hand is pushing the drug and the resilience of the skinwill start to push the bottom half of the device (part not held in hand)back towards the hand. This may result in a less good seal with the skinand, in theory, if the hand force stops immediately the snap tabs arebroken then the drug would never be pushed from the device - they relyon the inertia in the hand to make the injection. In practice this meansthat the user pushes and pushes and then suddenly the tabs break and thedevice is pushed into the target possibly causing pain and bruising withthe device. In the present injection the skin is compressed by a steadyhand force. At the point of actuation the main spring controls thedelivery of the drug and the hand maintains (but does not suddenlyincrease) the force on the skin to ensure a good contact with the skin.If at any point before actuation the sensation on the skin is painfulthen the injection site can be altered or the injection aborted ratherthan causing further pain and/or bruising.

Devices of the type described have been demonstrated by the applicant tobe capable of delivering a drug as demonstrated by the followingexamples:

EXAMPLES

Initial experiments were carried out with non pharmaceutical materialsto demonstrate the delivery concept. These experiments comprised thefollowing:

Example 1 Drug Splinters

A rod of 0.9 mm diameter pencil lead was broken to lengths ofapproximately 6 mm and a point was sanded on one end of each length anda flat on the other to create solid splinters. The splinters were placedin the drug package shown in FIG. 19 and successfully administered topig skin using a prototype delivery system.

Example 2 Pioneer Projectile Followed by a Solid Rod

The same pencil lead detailed in example 1 above was cut into shortlengths of approximately 3 mm in length. These had a point sanded on oneend and a flat on the other end to create pioneer projectiles. Furtherrods of the same pencil lead were cut at approximately 4 mm in lengthand had both ends sanded flat. When a pioneer projectile and a solid rodwere placed in a drug package as shown in FIG. 19 they were successfullyadministered to pig skin using a prototype delivery system.

Example 3 Pioneer Projectile Followed by a Soft Rod

A soft rod of wax was extruded through a die and rods of approximately 4mm in length were cut with a flat at each end. Further sections were cutwith a point at one end and a flat at the other end. When a pointedsection (identical in shape and size to the splinter used in example 1)was administered to pig skin using a drug package as shown in FIG. 19the wax did not pierce the skin but was flattened on the skin surface.When a rod of the same waxy material was placed behind a pioneerprojectile used in example 2 and administered to pig skin using a drugpackage as shown in FIG. 19 then both the pioneer projectile and thewaxy material were successfully delivered into the tissue. The waxmaterial used for this experiment could easily be squashed between afinger and a thumb.

Example 4 Pioneer Projectile Followed by Solid Beads.

Beads of diameters 0.5-0.75 mm were placed in a drug package, as shownin FIG. 19, behind a pioneer projectile as detailed in example 2. Thepioneer projectile and all the beads were successfully administered topig skin using a prototype delivery system.

The experiments outlined above demonstrated that a range of differentmaterials could be delivered behind a solid pioneer projectile. Ideallyit is preferred that the pioneer projectile is manufactured frompharmaceutical grade compounds that will dissolve in the target tissue.Two processes have been used to produce such pioneer projectiles asoutlined below:

Example 5

A hot melt of sugars is produced which can then be moulded into thecorrect form for a pioneer projectile or extruded to produce long rod.If an extrusion process is used then the pioneer projectiles can be cutto shape from the soft extrudate or the sharp ends of the pioneerprojectile can be formed when the extrudate has solidified. This processproduces a material similar to a boiled sweet which can be very hard andincorporate a sharp point on one end.

Example 6

A mix of powders is produced using pharmaceutical grade sugars togetherwith a hardening agent such as polyvinylpyrolidone (PVP). The powderblend is extruded through a die to produce a long rod of the compound.Some blends require a lubricant to facilitate the extrusion and bindingprocess such as water or ethanol. The pioneer projectiles are formed bycutting the long rod into short sections. This process can befacilitated by using a hot knife. If necessary, the point or flat end ofthe pioneer projectile can be created by sanding or filing a short rodof the extrudate.

1. A drug delivery device comprising: i) a housing; ii) a generator of aforce capable of pushing a drug from a packaging into a human or animalbody; iii) a transmitter of said force to push the drug from thepackaging into the human or animal body; and iv) a device for triggeringthe device.
 2. A drug delivery device as claimed in claim 1 wherein thehousing defines: i) an upper barrel at one end of the device whichhouses the generator; and ii) a lower barrel, at the end remote from theupper barrel, which houses: a) a packaged drug; and b) the transmitterto push the drug from the packaging said lower barrel being in operativecommunication with said upper barrel and said packaged drug.
 3. A drugdelivery device as claimed in claim 1 further comprising v) a receiverof the packaged drug; and vi) a priming element.
 4. A drug deliverydevice as claimed in claim 1 wherein the generator is capable ofgenerating a force of from 10-40N.
 5. A drug delivery device as claimedin claim 1 wherein the transmitter causes the drug to be pushed from thepackaging at less than 10 m/s.
 6. A drug delivery device as claimed inclaim 2 wherein said packaged drug (is slidably disposed in thereceiver.
 7. A drug delivery device as claimed in claim 2 wherein thepackaged drug is slidably disposed in the lower barrel and comprises apackaging containing a drug, said packaging comprising a housing havinga channel running there through in which is disposed a drive pin orother element, a skin piercing element and the drug; said housingfurther comprising i) a region allowing the packaged drug to be slidablymounted to the drug delivery device at the receiver; and ii) an endadapted to engage and tension the skin.
 8. A drug delivery device asclaimed in claim 1 wherein the skin piercing element is a pioneerprojectile, a syringe needle or the head of a drug splinter.
 9. A drugdelivery device as claimed in claim 1 wherein the drive pin or otherelement has a flat or enlarged head.
 10. A drug delivery device asclaimed in claim 1 further comprising a resilient element below orotherwise in association with the drive pin or other element to ensurethe drive pin is withdrawn after use.
 11. A drug delivery device asclaimed in claim 1 wherein the generator is a spring.
 12. A drugdelivery device as claimed in claim 11 wherein the spring is a coil orgas spring.
 13. A drug delivery device as claimed in claim 11 whereinthe force generated by the spring is adjustable.
 14. A drug deliverydevice as claimed in claim 1 wherein the transmitter is a striker.
 15. Adrug delivery device as claimed in claim 14 wherein a region of thestriker is shaped to fit a correspondingly shaped surface in a wallseparating the upper and lower barrels defined by the housing such thatthe striker is aligned to strike the drive pin or other element in thepackaged drug on actuation.
 16. A drug delivery device as claimed inclaim 14 wherein the striker comprises a substantially frustoconicalshoulder region which engages a substantially frustoconical surface inthe wall separating the upper and lower barrels defined by the housing.17. A drug delivery device as claimed in claim 14 wherein the packageddrug and striker are slidably mounted in the device such that the devicecan be can be primed by pushing the device against the skin.
 18. A drugdelivery device as claimed in claim 2 wherein the device comprises aslewing spring, a sliding piston having an aperture therein and thestriker, all housed in the lower barrel and the device is triggered bythe sliding of the piston up the lower barrel until shoulder region ofthe striker engages shaped surface and aligns the striker with theaperture in the sliding piston such that the striker moves down theaperture under the action of the generator.
 19. A drug delivery deviceas claimed in claim 2 wherein the device is primed and actuated by asingle action.
 20. A device as claimed in claim 19 wherein pushing thepackaged drug up the lower barrel with sufficient force causes thedevice to be primed and actuated.
 21. A device as claimed in claim 19wherein the action of pushing the packaged drug up the lower barrel withsufficient force causes the sliding piston to move up the lower barrelthereby causing the striker to be pushed up the lower barrel out of afirst position in which it is not axially aligned with the aperture inthe sliding piston which operatively communicates with the packaged drugand at the same time acts on a spring follower in the upper barrelcausing the spring to be compressed and the device primed such that whenthe required delivery force is generated the striker is axially alignedwith the aperture of the sliding piston and is thus actuated such thatthe spring acts through the spring follower and striker upon the drivepin or a like element in the packaged drug to deliver the drug into thehuman or animal body.
 22. A device as claimed in claim 1 wherein thedevice is primed and actuated by two separate actions.
 23. A drugdelivery device as claimed in claim 2 wherein the upper barrel and lowerbarrel are formed as separate components.
 24. A drug delivery device asclaimed in claim 1 wherein the drug is in a contained form.
 25. A drugdelivery device as claimed in claim 24 wherein the drug is either: aliquid contained by a membrane; a liquid with a viscosity of at least500 centipoises, more preferably at least 5000 centipoises, and morepreferably still at least 100,000 centipoises; a semi solid, a paste, agel or a solid.
 26. A drug delivery device as claimed in claim 1 furthercomprising a packaged drug as an integral part oftile device.
 27. A drugdelivery device as claimed in claim 1 in which the device and/orpackaged drug is sealed in a foil pouch or the like to prevent ingressat: for example, moisture, oxygen, light, bacteria or other drugdegrading or contaminating agents.
 28. A drug delivery device as claimedin claim 1 wherein the tip of the pioneer projectile or needle ispositioned a few mm in from end of the packaging such that it is movingwhen contacting the skin.
 29. A drug delivery device as claimed in claim1 wherein the end about the exit of the channel is in the form of asubstantially annular ring located immediately about the channel exitand having a depth and width in the range 1.5 mm to 6 mm.
 30. A drugdelivery device as claimed in claim 1 further comprising a positive lockretention system to ensure the packaged drug does not come away from thedevice under gravity yet is free to slide up the device.
 31. A singleuse drug delivery device comprising: i) a housing; ii) a pre-primedgenerator to generate a force capable of pushing a drug from a packaginginto a human or animal body; iii) a transmitter to transmit said forceto push the drug from the packaging into the human or animal body; iv) apackaged drug forming an integral part of the device; and v) a triggerdevice.
 32. A device as claimed in claim 31 wherein the trigger deviceis an actuation button or like element.
 33. A packaged drug, for usewith a drug delivery device, comprising a packaging containing a drug,said packaging comprising a housing having a channel running therethrough and in which is disposed a drive pin or other element, a skinpiercing element, and the drug, said housing further comprising i) aregion allowing the packaged drug to be slidably mounted to the drugdelivery device; and ii) an end adapted to engage and tension the skin.